TY - JOUR
TI - A Th1/IFNG gene signature is prognostic in the adjuvant setting of resectable high-risk melanoma but not in non-small cell lung cancer
AU - Dizier, B.
AU - Callegaro, A.
AU - Debois, M.
AU - Dreno, B.
AU - Hersey, P.
AU - Gogas, H.J.
AU - Kirkwood, J.M.
AU - Vansteenkiste, J.F.
AU - Sequist, L.V.
AU - Atanackovic, D.
AU - Goeman, J.
AU - van Houwelingen, H.
AU - Salceda, S.
AU - Wang, F.
AU - Therasse, P.
AU - Debruyne, C.
AU - Spiessens, B.
AU - Brichard, V.G.
AU - Louahed, J.
AU - Ulloa-Montoya, F.
JO - Clinical Cancer Research
PY - 2020
VL - 26
TODO - 7
SP - 1725-1735
PB - American Association for Cancer Research Inc.
SN - 1078-0432
TODO - 10.1158/1078-0432.CCR-18-3717
TODO - gamma interferon;  tumor marker, adult;  Article;  cancer prognosis;  cancer surgery;  controlled study;  disease free survival;  high risk patient;  human;  lymph node metastasis;  major clinical study;  melanoma;  non small cell lung cancer;  overall survival;  priority journal;  prospective study;  protein expression level;  Th1 cell;  tumor associated leukocyte
TODO - Purpose: Immune components of the tumor microenvironment (TME) have been associated with disease outcome. We prospectively evaluated the association of an immune-related gene signature (GS) with clinical outcome in melanoma and non-small cell lung cancer (NSCLC) tumor samples from two phase III studies. Experimental Design: The GS was prospectively validated using an adaptive signature design to optimize it for the sample type and technology used in phase III studies. One-third of the samples were used as “training set”; the remaining two thirds, constituting the “test set,” were used for the prospective validation of the GS. Results: In the melanoma training set, the expression level of eight Th1/IFNg-related genes in tumor-positive lymph node tissue predicted the duration of disease-free survival (DFS) and overall survival (OS) in the placebo arm. This GS was prospectively and independently validated as prognostic in the test set. Building a multivariate Cox model in the test set placebo patients from clinical covariates and the GS score, an increased number of melanoma-involved lymph nodes and the GS were associated with DFS and OS. This GS was not associated with DFS in NSCLC, although expression of the Th1/IFNg -related genes was associated with the presence of lymphocytes in tumor samples in both indications. Conclusions: These findings provide evidence that expression of Th1/IFNg genes in the TME, as measured by this GS, is associated with clinical outcome in melanoma. This suggests that, using this GS, patients with stage IIIB/C melanoma can be classified into different risk groups. © 2019 American Association for Cancer Research.
ER -